REBEL Cast Ep103: Outpatient COVID-19 Therapy

I was fortunate enough to record a podcast on Rob Orman’s, Stimulus podcast on Oct 14th, 2021.  We both felt it was an important enough topic that we should post it on both his and my site.  The treatment of non-hospitalized patients suffering from COVID-19 is a hot topic and constantly changing.  In this podcast Rob and I dive into the literature of outpatient treatment.  We discuss which subgroups of patients might benefit from monoclonal antibodies, why the jury is still out on the benefit of ivermectin, the role of inhaled budesonide, and outpatient anticoagulation which hasn’t been studied robustly, but hopefully will be someday.

REBEL Cast Ep103: Outpatient COVID-19 Therapy

  • The Best Treatment of COVID-19 is Prevention Through Vaccination:
    • “Study after study has shown that the risks of bad things happening are much worse if you get COVID than if you get the vaccine.”
  • Monoclonal Antibodies:
    • RECOVERY Trial: Giving monoclonal antibodies to everyone with COVID, doesn’t appear to have much benefit
    • The subgroup of patients who do benefit from monoclonal antibodies are those without a robust immune response (i.e seronegative patients). This includes patients who are immunocompromised, elderly, have comorbid disease
    • The benefit of monoclonal antibodies in survival and disease severity was only present in patients who were seronegative
    • The problem in the US is we are not checking for seronegativity, so we estimate the patient’s risk to determine if this multi-thousand dollar medication should be given
    • Initially at my shop we were using bamlanivumab, but it seems the monoclonal antibodies that use multiple types of antibodies work better (i.e. Regeneron)
    • We are currently only offering REGN-CoV2 (Regeneron mAb cocktail) to patients who are high risk and early in the disease process
    • Early on we were trying to meet the demands of everyone who wanted it, but then supplies started to diminish and we were running out of this medication for those who needed it most.
    • The irony of people demanding monoclonal antibodies, but refusing vaccination because they don’t know what’s in it:
    • “You know what else we don’t know exactly what’s in it? Chicken McNuggets.  There’s so many things in life that we don’t really know what’s in it. But yet we take it.  Unfortunately, many people draw the line at the COVID vaccine.”
  • Why We Can’t Trust Everything We Read About COVID Therapy in News Headlines:
    • “The plural of anecdote is not data.” Just because you believe something works or you think you’re seeing a positive effect from it doesn’t mean that it actually works.  You need a randomized controlled trial to compare a therapy with placebo to ensure that it’s the drug and not another variable which is having the impact
    • When making decisions about therapies, you need to do do your own research (which is not the same as listening to someone’s opinion on YouTube or reading a newspaper).  You must look at the studies, the outcomes, the methodology, and then make a scientific decision based on that evidence
  • Ivermectin:
    • Using ivermectin studies as an example, there have been 30 to 40 trials and the one that was most methodologically sound was pulled due to falsified data (Link is HERE)
    • While the headline might read, “Ivermectin Works,” the truth is that oftentimes confounding factors, something other than the ivermectin, are what’s making the difference
    • Meta-analyses that continue include this data show benefit, but those that exclude it show no ivermectin benefit
    • Even if we believed that ivermectin works, there’s still so much we don’t know about it.  What is the ideal dose and duration of therapy?
  • Inhaled Budesonide:
    • The STOIC Trial: randomized patients to inhaled budesonide vs no budesonide and found no improvement in mortality or severity of disease, but there was improvement in symptoms
    • I prescribe budesonide to COVID-19 patients who have symptoms of dyspnea but don’t have hypoxemia.
  • The Slippery Slope of Outpatient Anticoagulation:
    • 2 multi-platform, controlled trials were published on the topic of anticoagulation.  One looked at COVID-19 patients who were critically ill (i.e. required ICU level of care) and the other included only non-critically ill patients (i.e. hospitalized, but not in the ICU).  Of note, any patient who required HFNC, NIV or greater was considered ICU level of care
    • The study of critically ill patients showed that therapeutic anticoagulation (compared to prophylactic) caused harm in these sicker patients, primarily due to bleeding complications. So the recommendation is prophylactic anticoagulation for patients requiring ICU level of care
    • The study of non-critically ill patients (those who could be managed with nasal cannula, non-rebreathers, or oxymizers) appears to benefit from therapeutic anticoagulation I’m terms of severity of disease and mortality
    • Why might this be?  My conjecture is that COVID-19 patients get caught in a vicious cycle of hypoxemia which leads to pulmonary vasoconstriction which further leads to worsening hypoxemia.  In addition, COVID-19 is a disease of vascular endothelium.  So, if you can anticoagulant patients early enough, before they have micro thrombi, then they’ll get less hypoxemia, less pulmonary vasoconstriction, and a greater chance of clinical improvement
    • The slippery slope is wondering about the potential benefit of outpatient anticoagulation
  • Things I Might Consider, as of Today, if I had a Symptomatic COVID-19 Patient that is Well Enough to Be Managed as an Outpatient:
    • Awake Prone Position: Proning while awake and definitely prone while sleeping
    • Incentive Spirometry: May help in recruitment of alveoli
    • Inhaled Budesonide: May help with symptomatology
    • Antioxidants: No evidence for this…BUT…Vitamin C, Vitamin D, Melatonin. They may help, readily available, cheap, and likely wouldn’t hurt

Post-Peer Reviewed By: Anand Swaminathan, MD (Twitter: @EMSwami)

Cite this article as: Salim Rezaie, "REBEL Cast Ep103: Outpatient COVID-19 Therapy", REBEL EM blog, November 15, 2021. Available at:

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